1. Field of the Invention
The present invention relates generally to the preparation and use of biocompatible implant compositions. More particularly, the present invention relates to injectable ceramic implant compositions for soft and hard tissue repair and augmentation.
The use of collagen compositions for tissue repair and augmentation is known. The collagen may be utilized in a variety of forms, including cross-linked and non-cross-linked fibrillar collagens, gelatins, and the like, and may be combined with various other components, such as lubricants, osteogenic factors, ceramic particles, and the like, depending on the intended use. For soft tissue repair, suspensions of fibrillar collagen have often been used by injecting the composition to a treatment site through a fine gauge needle. For bone and hard tissue repair, fibrillar collagens have been combined with the ceramic powders, such as hydroxyapatite and other calcium phosphates. These compositions, however, have not been injectable.
The use of fibrillar collagen as the primary matrix material in injectable soft and hard tissue implant compositions has several limitations. The preparation of fibrillar collagen suitable for human use is relatively time consuming and expensive. In particular, the complete removal of contaminating and potentially immunogenic substances to produce "atelocollagen" is a relatively complex and expensive procedure. Moreover, the persistence, shape retention, cohesiveness, stability, elasticity, toughness, and intrudability of the fibrillar collagen compositions could be improved.
Heretofore, fibrillar and other collagens have been used primarily for superficial soft tissue augmentation, i.e., near the surface of the skin. For deep tissue injection, particularly to locations near bone and cartilage, the use of cross-linked collagens is problematic, and the use of non-cross-linked collagens is ineffective.
One approach for improving the compositions utilized for soft and hard tissue repair and augmentation would be to at least partly replace the fibrillar collagen in such formulations with a ceramic mineral material, particularly with hydroxyapatite or other calcium phosphate minerals. Hydroxyapatite has very low immunogenicity.
The incorporation of such mineral particles in compositions intended for soft and hard tissue treatment, however, has been found to be ineffective due to the difficulty in introducing such compositions to the treatment site. In particular, the incorporation of generally available ceramic mineral particles inhibits or prevents the introduction of the compositions through a fine gauge needle to the tissue site of interest. Thus, injectable ceramic implant materials have generally not been available and any benefits which may derive from their use remain speculative.
It would therefore be desirable to provide improved injectable implant materials for soft and hard tissue repair and augmentation where at least a portion of the primary tissue matrix substance is a biocompatible ceramic material. Such compositions should be readily injectable so that they can be introduced to a desired soft tissue site using a fine gauge needle. In addition, such compositions should be persistent at the site of injection, preferably adhering to the soft tissue into which they have been injected; they should be stable, i.e. undergo no significant changes in situ; be tough and elastic, i.e. be capable of bearing loads without undergoing excessive or permanent deformation; be nontoxic and well-tolerated by the body, i.e., produce no or tolerable levels of immune and inflammatory responses; and be intrudable, i.e., form a relatively dispersed, irregularly shaped mass within the tissue where the composition has been introduced. In particular, the improved implant materials should be suitable for deep tissue injection, particularly to locations near bone and cartilage, for purposes such as sphincter repair, nasal repair, and the like. It will be appreciated, of course, that the compositions and methods of the present invention while meeting at least some of these objectives, will not necessarily meet each of these objectives in every embodiment.
2. Description of the Background Art
Compositions comprising collagen and a mineral material, such as hydroxyapatite or tricalcium phosphate, are known for use in repairing bone defects. See, for example, U.S. Pat. Nos. 5,001,169; 4,992,226 (which is a division of 4,795,467); 4,865,602; 4,776,890; and 4,563,350. Lemons et al. Second World Congress of Biomaterials, Apr. 27-May 1, 1984, reported the use of collagen and hydroxyapatite/calcium phosphate compositions to repair bone lesions in rabbits. A soon to be commercially available composition with the trade name COLLAGRAFT (Zimmer, Inc., Warsaw, Ind.) comprises highly purified bovine dermal collagen which is combined with hydroxyapatite and tricalcium phosphate at a ratio of about 1:15 collagen: ceramic by dry weight. Such collagen and mineral formulations are generally not injectable through a small diameter needle and have not been employed for soft tissue repair.
U.S. Pat. No. 4,803,075, describes collagen compositions including a lubricant material to enhance injectability through narrow diameter needles for soft tissue repair. U.S. Pat. No. 4,863,732, describes an injectable composition comprising collagen and an osteogenic factor suitable for bone repair. POLYTEF.RTM. Paste (Mentor Corporation, Santa Barbara, Calif.) is an injectable paste composition comprising pyrolyzed poly(tetrafluroethylene) particles present in glycerin with a small amount of polysorbate 20 suitable for tissue repair of the larynx.
Hydroxyapatite layers on various surgical implants have been found to enhance bonding to soft tissue in a host. Hench, "Bioglass Implants for Otology," in: Biomaterials in Otology, Grote, ed., pp. 62-69, Martinus Nijhoff Publishers, The Hague (1983).
The full disclosures of each of these references are incorporated herein by reference.